title: Ex vivo imaging of pancreatic beta cells using a radiolabeled GLP-1 receptor agonist.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the binding specificity of the radiolabeled glucagon-like peptide 1 receptor (GLP-1R) agonist (Lys⁴⁰(DOTA)NH₂)Exendin-4 in the pancreas using a combination of ex vivo autoradiography and immunohistochemistry.
  
  
  METHODS
  Sprague-Dawley rats were administered [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 i.v. with or without unlabeled Exendin (9-39) to determine binding specificity. Similar experiments were performed using Zucker diabetic fatty (ZDF) and Zucker lean (ZLC) rats. Animals were euthanized and the pancreas was extracted, immediately frozen, and sectioned. The sections were apposed to phosphor imaging plates, scanned, and immunostained for insulin.
  
  
  RESULTS
  Co-registration of the autoradiographic and immunohistochemical images revealed that [⁶⁴Cu] (Lys⁴⁰(DOTA)NH₂)Exendin-4 specific binding was restricted to islet cells. This binding was blocked by the co-administration of Exendin(9-39) indicating that the radiotracer uptake is mediated by GLP-1R. Uptake of [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 was greatly decreased in the pancreas of ZDF rats.
  
  
  CONCLUSIONS
  Ex vivo autoradiography results using [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 suggest that GLP-1R agonists based on Exendin-4 are attractive PET ligands for the in vivo determination of β-cell mass.
authors.affiliation: Department of Imaging, Merck Research Laboratories, West Point, PA 19486, USA. brett_connolly@merck.com
authors.forename: Brett M
authors.initials: BM
authors.lastname: Connolly
authors.forename: Amy
authors.initials: A
authors.lastname: Vanko
authors.forename: Paul
authors.initials: P
authors.lastname: McQuade
authors.forename: Ilonka
authors.initials: I
authors.lastname: Guenther
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Meng
authors.forename: Daniel
authors.initials: D
authors.lastname: Rubins
authors.forename: Rikki
authors.initials: R
authors.lastname: Waterhouse
authors.forename: Richard
authors.initials: R
authors.lastname: Hargreaves
authors.forename: Cyrille
authors.initials: C
authors.lastname: Sur
authors.forename: Eric
authors.initials: E
authors.lastname: Hostetler
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods*; D003301:Copper Radioisotopes; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006573:Heterocyclic Compounds, 1-Ring; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D014688:Venoms / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D003301:Copper Radioisotopes; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D006573:Heterocyclic Compounds, 1-Ring; D010455:Peptides; D019275:Radiopharmaceuticals; D018027:Receptors, Glucagon; D014688:Venoms; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D000077270:Exenatide